APPENDICES - NIHR Health Technology Assessment Programme

188
Appendix 13
Study details Population details Treatment details Results Interpretation
Authors’ conclusions PDT using a
1-hr incubation with 160 mg/g MAL
cream may have potential for treating
relatively mild AK lesions and offers
practical advantages, but regular
substitution is not recommended
Brief study appraisal As the authors
acknowledge, there were some
important flaws in the design of this
study, including the lack of blinding of
outcome assessors, and having response
rate judgements made clinically rather
than histologically. Although the mean
incubation and illumination times were
consistent according to the protocol,
it was clear that a large proportion of
patients received only 1 PDT session
(when 2 are recommended) and
around one-third of lesions had not
been debrided. Given that the protocol
does not appear to have been followed
closely, or has not utilised PDT optimally,
these results should be considered with
caution. No p-values or formal tests of
statistical significance appear to have
been carried out, making it difficult to
assess the real differences between
treatment groups
Morbidity Lesion response (based on
110 patients with 380 lesions, two patients
with four lesions excluded due to wrong
diagnosis). Overall lesion response (not
clear if CR) 85% 3 hr + 160 mg/g 76%
1 hr + 160 mg/g 74% 3 hr + 80 mg/g 77%
1 hr + 80 mg/g. Note: About one-third of
lesions were not debrided as per protocol.
For the 3 hr + 160 mg/g group CR was
higher for debrided lesions (89%) than nondebrided
(78%)
Lesion recurrence (evaluated in 97 patients
with 299 lesions that had responded
completely): The lowest recurrence rates
occurred in the 3 hr + 160 mg/g group (11%)
compared with between 26% and 45% for
the other groups
Patients who received two PDT sessions:
Lesion recurrence was lower for the 1-hr
and 3 hr + 160 mg/g groups (19% and 17%)
than for the 80 mg/g groups (44–45%). For
debrided lesions in the 3 hr + 160 mg/g
recurrence was 10% vs 14% for nondebrided
lesions
QoL and return to normal activity
Cosmetic outcome (assessed by VAS score
at 12 mth) was rated at between 8.4 cm and
9.3 cm by both investigator and patients
indicating an excellent cosmetic outcome
AEs Most AEs were mild intensity and the
majority were local. The most commonly
reported AE was erythema with a median
duration of 17 d. Other AEs included skin
pain, pruritis, burning sensation on skin,
oedema and suppuration. Four patients
experienced SAEs but these were not
considered to be treatment related
Treatment-related AE %:
1 hr + 160 mg/g, 98%
3 hr + 160 mg/g, 99%
1 hr + 80m/g, 98%
3 hr + 80 mg/g, 96%
Trial treatments MAL–PDT comparing
incubation time (1 hr or 3 hr) and dose
(160 mg/g or 80 mg/g)
Intervention MAL–PDT
(1 hr + 160 mg/g). Most lesions were
prepared using dermal curette to remove
scales and crusts. 1-mm-thick layer of
MAL cream applied to each lesion and
to 5 mm of surrounding area. Lesions
covered with occlusive dressing for
specified incubation period then wiped
off with saline. Lesions were illuminated
with red lamp light (wavelength 570–
670 nm, intensity 70 – 190 mW/cm2 )
to provide total light dose of 75 J/cm2 .
The mean illumination time was around
9.5 min. Any lesions without CR at 2 or
3 mth were given 2nd PDT treatment.
Any non-CR at 6 mth offered alternative
treatment
Comparator MAL–PDT
(3 hr + 160 mg/g) as above
2nd comparator MAL–PDT
(1 hr + 80 mg/g) as above
3rd comparator MAL–PDT
(3 hr + 80 mg/g) as above
Treatment intention
Curative
Type(s) of lesion and
histology Primary AK
Main eligibility criteria
Patients of 18 yr or older
with Fitzpatrick skin type
I, II or II with primary
previously untreated,
non-pigmented and noninfiltrating
AK lesions (up
to four lesions). Extensive
exclusion criteria were
reported
Patient characteristics
% Male: 56, age not
reported. The majority of
patients had three or fewer
lesions; most were located
on the face/scalp and were
thin or moderately thick
Concomitant
treatment Not stated
Authors Braathen et
al. (2008) 54
Data source Full
published paper
Country Not stated,
‘Europe’
Language English
Study design RCT
No. of participants
Total: 119
randomised, 112
treated (384 lesions)
Intervention: 28 (1 hr;
160 mg/g)
Comparator: 30
(3 hr; 160 mg/g)
2nd Comparator: 25
(1 hr; 80 mg/g)
3rd Comparator: 29
(3 hr; 80 mg/g)
No. of recruiting
centres Eight
Follow-up period
and frequency FU
at wk 1 and 2, then
at 2, 3, 6 and 12 mth
d, day(s); hr, hour(s); mth, month(s); wk, week(s); yr, year(s).